Details for: UNC5B

Gene ID: 219699

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: UNC5B

Ensembl ID: ENSG00000107731

Description: unc-5 netrin receptor B

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 13.28
    rCSI 41.52%
    PRS 68.54
  • endothelial cell of vascular tree CL0002139
    CSI 8.26
    rCSI 45.18%
    PRS 78.42
  • ciliated epithelial cell CL0000067
    CSI 7.49
    rCSI 6.59%
    PRS 71.53
  • type EC enteroendocrine cell CL0000577
    CSI 5.68
    rCSI 20.16%
    PRS 85.65
  • pancreatic stellate cell CL0002410
    CSI 5.3
    rCSI 30.83%
    PRS 85.42
  • blood vessel endothelial cell CL0000071
    CSI 4.96
    rCSI 10.29%
    PRS 78.84
  • pancreatic D cell CL0000173
    CSI 4.4
    rCSI 4.33%
    PRS 84.35
  • sncg GABAergic cortical interneuron CL4023015
    CSI 4.24
    rCSI 6.82%
    PRS 66.01
  • bronchus fibroblast of lung CL2000093
    CSI 4.14
    rCSI 3.36%
    PRS 81.41
  • cardiac endothelial cell CL0010008
    CSI 4.09
    rCSI 16.52%
    PRS 81.96
  • secretory cell CL0000151
    CSI 4
    rCSI 4.17%
    PRS 81.31
  • colon epithelial cell CL0011108
    CSI 3.83
    rCSI 4.01%
    PRS 79.47
  • cytotoxic T cell CL0000910
    CSI 3.39
    rCSI 19.43%
    PRS 84.7
  • pulmonary capillary endothelial cell CL4028001
    CSI 3.2
    rCSI 6.1%
    PRS 90.82
  • cerebral cortex endothelial cell CL1001602
    CSI 2.99
    rCSI 5.18%
    PRS 73.99
  • fallopian tube secretory epithelial cell CL4030006
    CSI 2.81
    rCSI 2.71%
    PRS 81.41
  • choroid plexus epithelial cell CL0000706
    CSI 2.76
    rCSI 4.52%
    PRS 71.79
  • Mueller cell CL0000636
    CSI 2.73
    rCSI 6.23%
    PRS 73.64
  • lung ciliated cell CL1000271
    CSI 2.72
    rCSI 3.14%
    PRS 74.57
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.7
    rCSI 3.23%
    PRS 64.71
  • innate lymphoid cell CL0001065
    CSI 2.67
    rCSI 5.51%
    PRS 78.45
  • stem cell CL0000034
    CSI 2.64
    rCSI 2.55%
    PRS 75.8
  • lung endothelial cell CL1001567
    CSI 2.57
    rCSI 5.99%
    PRS 91.38
  • respiratory suprabasal cell CL4033048
    CSI 2.57
    rCSI 3.29%
    PRS 84.9
  • pulmonary ionocyte CL0017000
    CSI 2.54
    rCSI 3.09%
    PRS 87.85
  • hepatic stellate cell CL0000632
    CSI 2.54
    rCSI 9.5%
    PRS 74.79
  • cerebellar granule cell CL0001031
    CSI 2.51
    rCSI 3.69%
    PRS 75.03
  • ON parasol ganglion cell CL4033052
    CSI 2.26
    rCSI 32.13%
    PRS 73.33
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 2.23
    rCSI 2.7%
    PRS 62.65
  • inhibitory interneuron CL0000498
    CSI 2.14
    rCSI 4.93%
    PRS 70.23
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 2.13
    rCSI 3.58%
    PRS 64.61
  • glycinergic amacrine cell CL4030028
    CSI 2.08
    rCSI 5.41%
    PRS 76.43
  • mesenchymal cell CL0008019
    CSI 2.04
    rCSI 5.19%
    PRS 75.7
  • conjunctival epithelial cell CL1000432
    CSI 1.87
    rCSI 2.85%
    PRS 82
  • peripheral nervous system neuron CL2000032
    CSI 1.8
    rCSI 2.45%
    PRS 73.89
  • club cell CL0000158
    CSI 1.79
    rCSI 2.62%
    PRS 76.74
  • BEST4+ enteroycte CL4030026
    CSI 1.75
    rCSI 2.17%
    PRS 82.74
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.71
    rCSI 3.02%
    PRS 64.05
  • basal cell of epidermis CL0002187
    CSI 1.71
    rCSI 3.03%
    PRS 51.09
  • cardiac muscle cell CL0000746
    CSI 1.65
    rCSI 2.37%
    PRS 72.04
  • vascular associated smooth muscle cell CL0000359
    CSI 1.62
    rCSI 5.26%
    PRS 80.08
  • retinal ganglion cell CL0000740
    CSI 1.57
    rCSI 3.47%
    PRS 68.23
  • intestinal tuft cell CL0019032
    CSI 1.54
    rCSI 2.35%
    PRS 85.36
  • retina horizontal cell CL0000745
    CSI 1.34
    rCSI 2.04%
    PRS 78.74
  • odontoblast CL0000060
    CSI 1.33
    rCSI 30.09%
    PRS 90.76
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.32
    rCSI 3.21%
    PRS 62.52
  • GABAergic amacrine cell CL4030027
    CSI 1.31
    rCSI 4.47%
    PRS 68.25
  • endothelial cell of uterus CL0009095
    CSI 1.22
    rCSI 8.92%
    PRS 89.33
  • regular atrial cardiac myocyte CL0002129
    CSI 1.22
    rCSI 3.92%
    PRS 78.76
  • helper T cell CL0000912
    CSI 1.16
    rCSI 1.64%
    PRS 80.41
  • basket cell CL0000118
    CSI 1.05
    rCSI 6.57%
    PRS 62.02
  • pancreatic PP cell CL0002275
    CSI 0.93
    rCSI 3.7%
    PRS 88.31
  • amacrine cell CL0000561
    CSI 0.85
    rCSI 2.45%
    PRS 71.71
  • pancreatic epsilon cell CL0005019
    CSI 0.81
    rCSI 3.79%
    PRS 89.29
  • blood vessel smooth muscle cell CL0019018
    CSI 0.78
    rCSI 6.33%
    PRS 76.63
  • glial cell CL0000125
    CSI 0.74
    rCSI 2.8%
    PRS 73.35
  • cardiac blood vessel endothelial cell CL0010006
    CSI 0.72
    rCSI 5.12%
    PRS 75.12

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [UNC5B](/details-gene/219699) (unc-5 netrin receptor B) is a protein-coding gene that encodes a transmembrane netrin receptor. As a key component of the Netrin signaling pathway, [UNC5B](/details-gene/219699) plays a fundamental role in processes such as axon guidance, angiogenesis, and the regulation of apoptosis. It functions as a dependence receptor, capable of inducing programmed cell death in the absence of its ligand, Netrin-1, a mechanism implicated in tumor suppression ([Link](https://doi.org/10.1073/pnas.0738063100)). **Overall**, expression data reveals its highest significance in specialized neuronal subtypes, such as the [chandelier pvalb GABAergic cortical interneuron](/details-cell/CL4023036), and broadly across various [endothelial cell of vascular tree](/details-cell/CL0002139) populations, underscoring its dual importance in nervous system development and vascular biology. ## Cellular Roles and Expression Landscape The expression profile of [UNC5B](/details-gene/219699) highlights its specialized functions in the nervous and vascular systems. **Overall**, the gene shows exceptional significance in the [chandelier pvalb GABAergic cortical interneuron](/details-cell/CL4023036) (CSI: 13.28), which is consistent with its well-defined role in axon guidance and neuronal development. Beyond the nervous system, [UNC5B](/details-gene/219699) is a prominent marker across a wide range of endothelial cell types. It is highly significant in [endothelial cell of vascular tree](/details-cell/CL0002139) (CSI: 8.26), [blood vessel endothelial cell](/details-cell/CL0000071) (CSI: 4.96), [cardiac endothelial cell](/details-cell/CL0010008) (CSI: 4.09), [pulmonary capillary endothelial cell](/details-cell/CL4028001) (CSI: 3.20), and [cerebral cortex endothelial cell](/details-cell/CL1001602) (CSI: 2.99). This widespread endothelial expression strongly supports its involvement in angiogenesis and the maintenance of vascular structures. The gene also demonstrates notable significance in various secretory and specialized epithelial cells, including [ciliated epithelial cell](/details-cell/CL0000067) (CSI: 7.49), [type EC enteroendocrine cell](/details-cell/CL0000577) (CSI: 5.68), and [pancreatic D cell](/details-cell/CL0000173) (CSI: 4.40), suggesting broader physiological roles beyond its primary functions in guidance and vascularization. Its moderate expression in [cytotoxic T cell](/details-cell/CL0000910) may also point to a potential, though less characterized, role in immune cell trafficking or function. ## Pathways and Molecular Function Functionally, [UNC5B](/details-gene/219699) is primarily characterized by its [netrin receptor activity](/details-pathway/GO:0005042). It is a central component of the [Netrin-1 signaling](/details-pathway/R-HSA-373752) and [Axon guidance](/details-pathway/R-HSA-422475) pathways, which are critical for [nervous system development](/details-pathway/R-HSA-9675108). Its high expression in cortical interneurons directly correlates with its involvement in [anterior/posterior axon guidance](/details-pathway/GO:0033564). A second major function of [UNC5B](/details-gene/219699) is its role as a dependence receptor in programmed cell death. In the absence of Netrin-1, [UNC5B](/details-gene/219699) can initiate an [apoptotic process](/details-pathway/GO:0006915). This is mediated through pathways such as '[Caspase activation via dependence receptors in the absence of ligand](/details-pathway/R-HSA-418889)', contributing to its putative role as a tumor suppressor ([Link](https://doi.org/10.1073/pnas.0738063100); [Link](https://doi.org/10.1038/sj.emboj.7600584)). Its localization to the [plasma membrane](/details-pathway/GO:0005886) and specifically within [membrane raft](/details-pathway/GO:0045121) microdomains is reportedly critical for this cell death-inducing activity ([Link](https://doi.org/10.1016/j.yexcr.2008.06.001)). The receptor's function in [angiogenesis](/details-pathway/GO:0001525) is likewise tightly controlled by Netrin-1 availability, linking vascular development to apoptotic regulation. ## Research Directions The dual, high-level expression of [UNC5B](/details-gene/219699) in both the central nervous system and the vasculature presents compelling avenues for future research. Its established role as a dependence receptor and putative tumor suppressor suggests its expression and activity are likely altered in pathological conditions such as cancer and neurodegenerative diseases. Based on the available data, several testable hypotheses can be proposed: 1. **[UNC5B](/details-gene/219699) mediates neuro-vascular crosstalk during cortical development.** Its high significance in both [chandelier pvalb GABAergic cortical interneuron](/details-cell/CL4023036) and [cerebral cortex endothelial cell](/details-cell/CL1001602) suggests it may function as a common receptor to co-pattern neuronal circuits and their supporting vasculature in response to shared Netrin-1 gradients. 2. **The apoptotic threshold for [UNC5B](/details-gene/219699) activation is cell-type specific.** The survival of [endothelial cell of vascular tree](/details-cell/CL0002139) versus neurons during development or tissue remodeling may depend on differential sensitivity to Netrin-1 withdrawal, potentially modulated by cell-specific co-receptors or intracellular signaling partners. 3. **Downregulation of [UNC5B](/details-gene/219699) in [colon epithelial cell](/details-cell/CL0011108) is a mechanism for apoptosis evasion in colorectal cancer.** Given its role as a tumor suppressor, loss of [UNC5B](/details-gene/219699) expression would allow epithelial cells to survive and proliferate in a low Netrin-1 environment, contributing to tumorigenesis. To test the first hypothesis regarding neuro-vascular crosstalk, a key experiment could involve a 3D organoid or co-culture system. Using human iPSC-derived cortical interneurons and cerebral endothelial cells, selective knockdown of [UNC5B](/details-gene/219699) in one or both cell types via CRISPR-Cas9 could be performed. Subsequent analysis of neuronal migration, synapse formation, and endothelial network complexity using high-resolution microscopy would reveal if [UNC5B](/details-gene/219699) is required for their coordinated development. As a therapeutic target, [UNC5B](/details-gene/219699) presents an interesting opportunity. Because it is a cell surface receptor that can induce apoptosis, strategies aimed at *activating* its pro-death signaling pathway could be effective in cancers where Netrin-1 is overexpressed as a survival factor. This could involve developing small molecules or biologics that block Netrin-1 binding or stabilize the unbound, death-inducing conformation of the receptor, thereby selectively targeting tumor cells dependent on the Netrin-1/[UNC5B](/details-gene/219699) axis for survival.

Genular Protein ID: 4191191963

Symbol: UNC5B_HUMAN

Name: Netrin receptor UNC5B

UniProtKB Accession Codes:

Q8IZJ1 Q5T3R9 Q5T3S0 Q86SN3 Q8N1Y2 Q9H9F3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CORUM 1 CTD 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 10 Ensembl 2 GO 9 Gene3D 4 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 14 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 5 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 3 RefSeq 2 SIGNOR 1 SMART 5 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12359238

Title: Modulation of G(ialpha(2)) signaling by the axonal guidance molecule UNC5H2.

PubMed ID: 12359238

DOI: 10.1016/s0006-291x(02)02277-5

PubMed ID: 12598906

Title: p53RDL1 regulates of p53-dependent apoptosis.

PubMed ID: 12598906

DOI: 10.1038/ncb943

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15164054

Title: The DNA sequence and comparative analysis of human chromosome 10.

PubMed ID: 15164054

DOI: 10.1038/nature02462

PubMed ID: 12655055

Title: The netrin-1 receptors UNC5H are putative tumor suppressors controlling cell death commitment.

PubMed ID: 12655055

DOI: 10.1073/pnas.0738063100

PubMed ID: 15729359

Title: The dependence receptor UNC5H2 mediates apoptosis through DAP-kinase.

PubMed ID: 15729359

DOI: 10.1038/sj.emboj.7600584

PubMed ID: 18582460

Title: Lipid raft localization and palmitoylation: identification of two requirements for cell death induction by the tumor suppressors UNC5H.

PubMed ID: 18582460

DOI: 10.1016/j.yexcr.2008.06.001

PubMed ID: 25374360

Title: FLRT structure: balancing repulsion and cell adhesion in cortical and vascular development.

PubMed ID: 25374360

DOI: 10.1016/j.neuron.2014.10.008

PubMed ID: 26235030

Title: Structural basis of latrophilin-FLRT-UNC5 interaction in cell adhesion.

PubMed ID: 26235030

DOI: 10.1016/j.str.2015.06.024

Sequence Information:

  • Length: 945
  • Mass: 103638
  • Checksum: 56064E335F323447
  • Sequence:
    • MGARSGARGA LLLALLLCWD PRLSQAGTDS GSEVLPDSFP SAPAEPLPYF LQEPQDAYIV 
KNKPVELRCR AFPATQIYFK CNGEWVSQND HVTQEGLDEA TGLRVREVQI EVSRQQVEEL 
FGLEDYWCQC VAWSSAGTTK SRRAYVRIAY LRKNFDQEPL GKEVPLDHEV LLQCRPPEGV 
PVAEVEWLKN EDVIDPTQDT NFLLTIDHNL IIRQARLSDT ANYTCVAKNI VAKRRSTTAT 
VIVYVNGGWS SWAEWSPCSN RCGRGWQKRT RTCTNPAPLN GGAFCEGQAF QKTACTTICP 
VDGAWTEWSK WSACSTECAH WRSRECMAPP PQNGGRDCSG TLLDSKNCTD GLCMQNKKTL 
SDPNSHLLEA SGDAALYAGL VVAIFVVVAI LMAVGVVVYR RNCRDFDTDI TDSSAALTGG 
FHPVNFKTAR PSNPQLLHPS VPPDLTASAG IYRGPVYALQ DSTDKIPMTN SPLLDPLPSL 
KVKVYSSSTT GSGPGLADGA DLLGVLPPGT YPSDFARDTH FLHLRSASLG SQQLLGLPRD 
PGSSVSGTFG CLGGRLSIPG TGVSLLVPNG AIPQGKFYEM YLLINKAEST LPLSEGTQTV 
LSPSVTCGPT GLLLCRPVIL TMPHCAEVSA RDWIFQLKTQ AHQGHWEEVV TLDEETLNTP 
CYCQLEPRAC HILLDQLGTY VFTGESYSRS AVKRLQLAVF APALCTSLEY SLRVYCLEDT 
PVALKEVLEL ERTLGGYLVE EPKPLMFKDS YHNLRLSLHD LPHAHWRSKL LAKYQEIPFY 
HIWSGSQKAL HCTFTLERHS LASTELTCKI CVRQVEGEGQ IFQLHTTLAE TPAGSLDTLC 
SAPGSTVTTQ LGPYAFKIPL SIRQKICNSL DAPNSRGNDW RMLAQKLSMD RYLNYFATKA 
SPTGVILDLW EALQQDDGDL NSLASALEEM GKSEMLVAVA TDGDC